Maternal and Neonatal Plasma Cytokine Levels in Relation to Mode of Delivery

Buonocore, Giuseppe; Filippo, M. De; Gioia, Dino; Picciolini, Enrico; Luzzi, Enrico; Bocci, Velio; Bracci, Rodolfo

doi:10.1159/000244225

Cited by 74 publications

(38 citation statements)

References 13 publications

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“…Preterm infants in this study were of relatively advanced gestational age, and no extremely premature infants of Ͻ28 weeks' gestational age were included, which may have had a considerable impact on our results. Decreased IL-8 levels in the infants delivered by ECS support observations stressing the role of labor as an important trigger of neonatal proinflammatory cytokine production (6). Recently, Jokic et al (12) found no relation between cytokine levels in cord blood serum and the mode of delivery.…”

Section: Discussionmentioning

confidence: 76%

Cell-Associated Interleukin-8 in Cord Blood of Term and Preterm Infants

Dembinski¹,

Behrendt²,

Heep³

et al. 2002

Clin Vaccine Immunol

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To assess the effect of gestational age and labor on the interleukin-8 (IL-8) concentration in whole cord blood and serum, IL-8 levels were determined simultaneously in cord blood serum and lysate in 134 infants. Following the elimination of some of the samples due to exclusion criteria, the data for 99 uninfected infants (71 term and 28 preterm) and 9 infants with neonatal bacterial infection delivered either vaginally or by elective or emergency cesarean section were analyzed. The effects of labor and gestational age were tested by analysis of variance. IL-8 was not detectable in the serum of 25 infants, whereas IL-8 levels in whole blood were measurable in all of the samples. The median IL-8 conncentrations in whole cord blood lysate were 106 pg/ml (range, 20 to 415 pg/ml) in preterm infants and 176 pg/ml (range, 34 to 1,667 pg/ml) in term infants. In contrast to the IL-8 levels in serum, IL-8 levels in whole blood were reduced after ECS. Gestational age had no independent effect on the IL-8 concentrations in either serum or whole blood; these concentrations increased in infected infants after labor. We conclude that the neonatal proinflammatory response to labor stress was more evident in the concentrations of IL-8 in whole blood than in serum. The levels of IL-8 in whole-blood lysate reflect proinflammatory stimulation in neonates and may be a useful diagnostic tool for the early diagnosis of neonatal infection.Interleukin-8 (IL-8) belongs to the class of proinflammatory "CC" chemokines defined by the position of two cysteine groups and is synthesized predominantly by monocytes. Its active form effectively activates neutrophil granulocytes, advancing the chemotaxis and synthesis of myeloperoxidase, thus suggesting a critical role in host defense to infectious diseases (1, 2).The IL-8 concentration in serum has been studied as a diagnostic marker of neonatal bacterial infection (NBI) (10, 11) and has been shown to be an early marker of neonatal bacterial infection, whereas the concentration of C-reactive protein (CRP) increases after 12 to 24 h in the course of systemic infectious disease. A "diagnostic gap " exists between the decline of IL-8 after 4 to 6 h and the increase in C-reactive protein at 12 to 24 h, which is a well-established marker of confirmed bacterial infection. Due to the rapid serum clearing of IL-8, its value as a monitoring parameter of infectious disease may be limited. In vivo, a large proportion of IL-8 is associated with erythrocytes and leukocytes (polymorphonuclear leukocytes and peripheral blood mononuclear cells), and the concentration in serum represents only a small fraction of the total amount of IL-8. The measurement of cell-associated IL-8 reflects more quantitatively its production and adds information regarding the stage of the disease and the patient's inflammatory response (7,9,13,14). Total IL-8 can be measured in whole blood after cell lysis with a good analytical test (16). In healthy adults, we previously observed an IL-8 peak level of Ͻ12 pg/ml with a median of 83 p...

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Section: Discussionmentioning

confidence: 76%

Cell-Associated Interleukin-8 in Cord Blood of Term and Preterm Infants

Dembinski¹,

Behrendt²,

Heep³

et al. 2002

Clin Vaccine Immunol

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“…Either no effect 42,43 or increased 44,45 neutrophil activation has been reported. However, plasma IL-8 46 , IL-6 concentration, and the reactive oxygen species release after zymosan stimulation of polymorphonuclear cells were increased in the umbilical cord blood of infants born after labor 47 , suggesting that the labor per se plays an important role in modulating host defense and might be an immunologically beneficial process for the neonates 39 . Our observation that fetal acidosis (cord blood pH less than 7.2) influences the NK cell percentage in umbilical cord blood is novel and requires further study.…”

Section: Journal Of Maternal-fetal and Neonatal Medicinementioning

confidence: 99%

Neonates born to pre-eclamptic mothers have a higher percentage of natural killer cells (CD3 - /CD56+16+) in umbilical cord blood than those without pre-eclampsia

White

Ahlstrand²

2003

DJMF

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Objective: Maternal endothelial dysfunction and intravascular inflammation have been implicated in the mechanisms of disease responsible for the clinical syndrome of pre-eclampsia. Recently, the activation of the innate limb of the immune response (neutrophils and monocytes) in the fetal circulation has been reported in neonates born to mothers with pre-eclampsia. Natural killer (NK) cells are identified morphologically as a subpopulation of lymphocytes, but functionally as one component of the innate immune system. NK cells participate in the control of viral or bacterial infection, regulation of hematopoiesis, production of cytokines and cytotoxicity of neoplastic cells. Accumulating evidence suggests that the innate system is required for mounting an adequate adaptive response. NK cells, originally defined as effector cells of the innate immune system, may also play a role as regulatory cells for the adaptive immune system. This study was designed to determine the proportion of the NK cell subset of lymphocytes in umbilical cord blood of neonates born to mothers with and without pre-eclampsia. Methods: A cross-sectional study including neonates of mothers with (n = 48) and those without pre-eclampsia (control group) (n = 72) was conducted. Pre-eclampsia was diagnosed in the presence of hypertension and proteinuria. The control group consisted of neonates (premature and term) with no evidence of acute inflammation within the extraplacental membranes (chorioamnionitis). Umbilical cord blood was collected at the time of delivery, and assayed using monoclonal antibodies for selective cluster differentiation (CD) antigens in order to determine the proportion of NK cells as a percentage of total lymphocytes. The immunophenotypic characteristic was determined using flow cytometry, and NK cells were identified by positivity of CD16 and CD56 without CD3 (CD3-/CD56+16+). Log transformation of the percentage of NK cells was performed. Parametric statistics were used for analysis. Multiple regression analysis was utilized to examine the contribution of potentially confounding factors on the proportion of NK cells. A p value of < 0.05 was considered statistically significant. Results: Neonates born to mothers with pre-eclampsia had a significantly higher percentage of NK cells (CD3-/CD56+16+) than those in the control group (pre-eclampsia, mean ± SD 17 ± 9% vs. control, mean ± SD 12 ± 7.5%; p = 0.001). Multiple regression analysis suggested that umbilical cord blood pH of < 7.2, labor with vaginal delivery and maternal pre-eclampsia were associated with an increased percentage of NK cells in umbilical cord blood. Conclusions: Pre-eclampsia is associated with a higher NK cell (CD3-/CD56+16+) subset of lymphocytes in umbilical cord blood than in the control group. This difference cannot be explained by fetal acidosis or the presence of labor.

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“…During pregnancy, the normal maternal immune response is a predominant T helper cell (T h 2) bias, allowing maternal partial tolerance of paternal MHC antigens present in foetal cells (Marzi et al, 1996;Wegmann et al, 1993). This T h 2 bias is reversed with birth of the baby (Buonocore et al, 1995) and during some intrauterine infections (Koga et al, 2009). Maternal CMV infection has been demonstrated to upregulate CCL2 and TNF-a in amniotic fluid from mothers of babies born with congenital CMV .…”

Section: Introductionmentioning

confidence: 99%

Stimulatory effects of human cytomegalovirus tegument protein pp71 lead to increased expression of CCL2 (monocyte chemotactic protein-1) during infection

Naing

Webel

Hamilton

et al. 2015

Journal of General Virology

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Human cytomegalovirus (CMV) is the most common infectious cause of congenital birth defects in developed countries. Studies of infected amniotic fluid and placentae show CMV infection leads to a pro-inflammatory shift in cytokine profiles with implications for pathogenesis of foetal disease. ELISA, immunofluorescence and real-time-PCR assays were used to investigate CCL2 (monocyte chemotactic protein-1) and TNF-a changes following CMV infection of human fibroblasts, as well as following transient expression of CMV gene products in HeLa cells. Infection of human fibroblasts with CMV AD169 resulted in increased cytoplasmic and extracellular expression of CCL2 during early stages of infection, followed by marked downregulation of the chemokine at late times. Induction of CCL2 was not observed with CMV clinical strain Merlin, consistent with the postulated immune-evasion potential of this genetically intact WT strain. Comparison between live and UV-irradiated virus infections showed that changes in CCL2 levels were a direct response to active CMV replication. There were no significant changes in TNF-a expression during a parallel time-course of CMV infection. In transient transfection assays, overexpression of CMV tegument protein pp71 resulted in intracellular and extracellular upregulation of CCL2 protein. mRNA analysis showed that pp71-induced elevation in CCL2 was mediated through transcriptional upregulation. The data showed that CMV-induced upregulation of CCL2 during early stages of infection was mediated, at least in part, by stimulation of viral pp71, which may contribute to viral pathogenesis through enhanced virus dissemination.

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Maternal and Neonatal Plasma Cytokine Levels in Relation to Mode of Delivery

Cited by 74 publications

References 13 publications

Cell-Associated Interleukin-8 in Cord Blood of Term and Preterm Infants

Cell-Associated Interleukin-8 in Cord Blood of Term and Preterm Infants

Neonates born to pre-eclamptic mothers have a higher percentage of natural killer cells (CD3 - /CD56+16+) in umbilical cord blood than those without pre-eclampsia

Stimulatory effects of human cytomegalovirus tegument protein pp71 lead to increased expression of CCL2 (monocyte chemotactic protein-1) during infection

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